Axial dependence of platelet-collagen interactions in flowing blood. Upstream thrombus growth impairs downstream platelet adhesion.

Abstract

Vascular subendothelium and collagenous surfaces were exposed to flowing cltrated blood. Platelet interactions with these surfaces were Investigated at various axial distances from the upstream end of the exposed surfaces. A pronounced axial decrease In surface coverage with platelets and in thrombus dimensions was encountered on collagenous surfaces. This phenomenon was observed at shear rates of 200 to 2000 s~\ but was most pronounced at low shear rates (<650 s~1). After 5 minutes of perfusion at a shear rate of 650 s~\ 4.6x10* platelets were deposited on the most upstream 20 mm 2 of the collagen surface, In contrast to 2.2x10° platelets/ 20 mm 2 14 mm farther downstream. Depletion of von Wlllebrand factor and/or thrombospondin from the boundary layer of the blood flow was not responsible for this. Collagen-bound von Wlllebrand factor enhanced the surface coverage with platelets without affecting the axial decrement, while pretreatment of the collagen surface with thrombospondin had no effect at all. However, partial Inhibition of thrombus growth by aspirin reduced the axial decrements, and less thrombogenlc surfaces as human and rabbit subendothelium, which induced only a few small thrombi, produced virtually no axial differences In platelet adhesion. Raising the shear rate to 2600 s~1 also gave no axial differences In platelet-collagen adhesion; It did, however, give an axial Increase In thrombus dimensions. This Increase was neutralized after the addition of antibody against human platelet thrombospondin to the blood. Our data are consistent with the view that platelet-surface Interactions are limited by the arrival of platelets to the surface at shear rates below 650 s~1. Surfaces that Induce rapid-growing upstream thrombi may deplete the boundary layer for platelets, resulting In decreased platelet adhesion and thrombus growth farther downstream. At higher shear rates, when the platelet supply to the surface Is not a limiting factor, thrombospondin released from upstream thrombi appears to enhance downstream thrombus growth and/or thrombus stability. (Arteriosclerosis 9:33-42, January/February 1989)

Mechanisms of arterial thrombosis in nonparallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental study in the pig model.

“…4), supporting the theory of platelet depletion from the boundary layer of the blood flow (22,23). A similar pattern of distribution was reported in platelet deposition on collagen-coated surfaces (24). At a shear rate of 850 s-' the distribution of platelets decreasing distally along the flow axis was less marked but still significant.…”

Dynamic monitoring of platelet deposition on severely damaged vessel wall in flowing blood. Effects of different stenoses on thrombus growth.

“…The reduced platelet reactivity in vitro could be due to platelet handling and recirculation as well as to absence of the influence by short-lived platelet-activating metabolites. 21 As to axial dependence patterns under in vitro conditions ( Figures 6A and 6E), the present results are in accordance with earlier in vitro and in vivo findings with perfusion times up to 30 minutes 7 and with the in vitro results by Sakariassen and Baumgartner 22 on collagen-coated surfaces and a short perfusion time (5 minutes). However, in in vivo perfusions there was no significant axial dependence of platelet deposition ( Figures 8B and 8D).…”

Effect of aspirin and epinephrine on experimentally induced thrombogenesis in dogs. A parallelism between in vivo and ex vivo thrombosis models.

“…tp<0.01, ip<0.05, compared before chamber 1. tions were prepared from Epon-embedded preparations at an axial position of 1 mm downstream from the flow inlet at the coverslip and perpendicular to the direction of blood flow. 20 The interactions were assessed by 1) standard morphometry and 2) computer-assisted morphometry.…”